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Drugs of abuse are small molecules that typically do not induce an antibody response following the administration. To induce antibodies against these kind of molecules, structural changes have to be made to obtain so called “haptens”. The hapten must be coupled to immunogenic proteins, called “carriers”. These connected derivatives are typically drug-linker adducts, in which the linker has a terminal functional group (i.e., carboxylic acid or aliphatic amine) that forms a covalent bond with the carrier. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Six nor-normorphine compounds were reacted with ethyl acrylate and ethyl bromoacetate. After the synthesis of the specific esters we hydrolyzed them to receive the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives. The next step was the coupling phase with glycine ethyl ester, but the reactions didn’t work or the work-up process was not accomplishable. As an alternative route the normorphine-compounds were reacted with N-chloroacetyl glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine sidechain. All of the glycine ester and the glycine carboxylic acid derivatives are under biological tests.

1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7–11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12–15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18–21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC50 values > 100 μg/mL).

Vilsmeier formylation of 2-(1-phenylhydrazonoethyl)naphtho(2,1-b)furan (2) gave 3-naphtho(2,1-b)furan-2-yl-1-phenyl-1H-pyrazole-4-carbaldehyde (3), which was reacted with C- and N-nucleophiles to afford naphthofuranpyrazol derivatives 4-8. Treatment of 2-((3-(naphtho(2,1-b)furan-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)- malononitrile (4a) with reactants having active hydrogen and Et3N gave the corresponding pyrazoline, pyran and chromene addition product derivatives 10, 12 and 13, consisting of three different connected heterocyclic moieties. Reaction of 1-((3-(naphtho(2,1-b)furan-2- yl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-phenylhydrazone (6b) with AcONa and ethyl bromoacetate or chloroacetone afforded the thiazolidinone and methylthiazole derivatives 14 and 15, respectively. In addition, intramolecular cyclization of 6d with Ac2O afford the corresponding 1,3,4-thiadiazol-2-yl acetamide derivative 16. The structures of the synthesized compounds were confirmed by IR, 1 H-NMR/ 13 C-NMR and mass spectral studies. Compound 14 showed promising effects against the tested Gram positive and negative bacteria and fungi.

Reaction of substituted acetophenone (hepta-O-acetyl-b-maltosyl)thiosemicarbazones with ethyl bromoacetate was investigated. It’s indicated that the nature of solvents and the catalysts affected the reaction yields, and that the microwave-assisted heating method gave higher yields of products than the conventional heating one. Based on the optimum conditions, ionic liquid [HOCH2CH2NH3+]‒OAc, dried chloroform and microwave-assisted heating, the synthesis of some 2-iminothiazolidin-4-ones containg maltose moiety were synthesized. Their structure have been confirmed by spectral data (FTIR, 1H NMR, 13C NMR and MS).

Reaction of substituted acetophenone (hepta-O-acetyl-b-lactosyl)thiosemicarbazones with ethyl bromoacetate was performed in the presence of anhydrous sodium acetate using microwave-assisted heating method. The reaction yields were 64-80%. Structure of 2-iminothiazolidin-4-one products was confirmed by spectroscopic methods. Isomer ratios 2 and 2' were determined by 1H NMR.